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Hyperleukocytosis in pertussis has a correlation with disease severity. We describe a 5-week-old infant with severe pertussis and hyperleukocytosis requiring mechanical ventilation. Baby developed refractory hypoxemia. Two cycles of exchange transfusion were done on different occasions. Exchange transfusion resulted in significant improvement in oxygenation and hemodynamic parameters. Exchange transfusion is a viable treatment option in pertussis hyperleukocytosis complicated by refractory hypoxemia or persistent features of Systemic Inflammatory Response Syndrome.